The overall objective of the proposed research is to obtain important information concerning the nature, control and products of tumors. The Zollinger-Ellison tumor (gastrinoma) is selected as the model for study because of the readily measured secretory product of these tumors (gastrin), important identified relationships between this and other tumors, and the demonstration of control mechanisms influencing tumor growth, hormone production, and release. Tumor product (gastrin) synthesis by Zollinger-Ellison tumor will be demonstrated and measured by techniques measuring incorporation of H3- amino acids into newly synthesized gastrin peptides using immunoadsorption purification techniques, and effects of a variety of hormones, calcium, and activators on gastrin synthesis by Zollinger- Ellison tumor will be determined. Gastrin release by Zollinger-Ellison tumor will be measured directly under controlled conditions and effects of calcium, hormones and activator substances on tumor gastrin release will be determined. Gastrin peptides contained in, synthesized by, and released by Zollinger-Ellison tumors will be characterized utilizing chromatographic and electrophoretic techniques, as well as immunochemical methods utilizing antibodies with precise specificity for limited areas of the gastrin molecule including those contained in and excluding the active site region. The significance and frequency of disappearance of metastasis of Zollinger-Ellison tumor following gastrectomy and its relationship to circulating levels of gastrin in the serum will be evaluated by radioimmunoassay. Relationships between secretin-stimulated gastrin release by Zollinger-Ellison tumors and calcium ion concentration will be evaluated by in vitro studies of tumor synthesis and release of gastrin and by in vivo studies measuring hormone (gastrin) release and plasma calcium concentrations in response to secretin administration.